Effects of acidosis and inorganic phosphate on Ca ²⁺ sensitivity of young and older adult skeletal muscle fibers

The cellular mechanisms for the age-related loss in skeletal muscle contractile function and increased fatigability are unresolved. We previously observed that the depressive effects of fatiguing levels of hydrogen (H⁺; pH 6.8, 6.6, and 6.2) and inorganic phosphate (P_i; 12, 20, and 30 mM) did not differ in myofibers from young compared with older adults. However, these studies used saturating Ca²⁺, while fatigue during high-intensity contractions in vivo also likely involves a decrease in myoplasmic free Ca²⁺. Thus, we compared the Ca²⁺ sensitivity of myofibers from 10 young (22.1 ± 3.6; 5 women) and 13 older (71.7 ± 5.5; 7 women) adults in conditions mimicking quiescent (pH 7 + 4 mM P_i) and fatigued (pH 6.2 + 30 mM P_i) muscle. Fast fiber cross-sectional area was ∼35% smaller in older (4,859 ± 2,116 µm²) compared with young (7,446 ± 2,399 µm², <i>P</i> = 0.002), which corresponded with lower maximal absolute force (P_o) in both quiescent (old = 0.75 ± 0.30 mN; young = 1.13 ± 0.32 mN; <i>P</i> = 0.002) and fatigue conditions (old = 0.35 ± 0.14 mN; young = 0.52 ± 0.16 mN; <i>P</i> = 0.002). There were no differences in fast fiber size-specific P_o, indicating the age-related decline in force was due to differences in fiber size. Elevated H⁺ and P_i shifted the force-pCa relationship to the right, confirming nonhuman studies that these metabolites contribute to fatigue by depressing the sensitivity of the myofilaments to Ca²⁺. However, Ca²⁺ sensitivity was not different with age or sex in either condition, and the metabolite-induced shift in the force-pCa relationship did not differ with age in either the slow (<i>P</i> = 0.507) or fast (<i>P</i> = 0.115) fibers. These data suggest the age-related increase in fatigability of limb muscles cannot be explained by an increased sensitivity of the myofibers to elevated H⁺ and P_i in maximal or submaximal Ca²⁺.<b>NEW & NOTEWORTHY</b> This study reports the effects of elevated H⁺ and P_i on Ca²⁺ sensitivity of human skeletal muscle fibers and determines whether the effects of these metabolites are altered by aging in submaximal Ca²⁺. The metabolites markedly depressed Ca²⁺ sensitivity in human muscle fibers, but there was no effect of age or sex. These data suggest that Ca²⁺ sensitivity is preserved with age in conditions that mimic both quiescent and fatigued muscle.